Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To test the hypothesis that tissue oxygen delivery would be affected by diminished oxygen stores in cyanotic congenital heart disease, serum ferritin, transferrin saturation, hemoglobin, red cell mean corpuscular volume (MCV), red cell 2,3-diphosphoglycerate (DPG), P50, blood gases, oxygen saturations and systemic oxygen transport were measured in 29 hypoxemic infants and children. For the group, aortic saturation was 81 +/- 9%, PaO2 was 50 +/- 12 mm Hg, hemoglobin 16.2 +/- 2.1 gm/dl and systemic oxygen transport 620 +/- 145 ml/min/m2. P50 was increased above normal values (28.8 +/- 2.3 vs 26.6 +/- 1.1 mm Hg, p less than 0.01), and DPG was 2.35 +/- 0.54 mumol/ml, at the upper limits of normal for this assay. Iron deficiency was present in 8. When patients with P50 greater than or equal to 30 mm Hg and P50 less than 30 mm Hg were compared, iron stores were diminished in the high P50 group: [serum ferritin (19 +/- 8 vs 53 +/- 48 ng/ml, p = 0.0006), transferrin saturation (11 +/- 6 vs 23 +/- 11%, p = 0.003) and MCV (79 +/- 8 vs 86 +/- 4 fl, p = 0.05)]. Hemoglobin, aortic oxygen saturation, PaO2 and systemic oxygen transport were similar in both groups. In children with iron sufficiency, 15 of 21 had MCV greater than 90th percentile for age and sex (p less than 0.001 versus expected distribution). Also, MCV greater than 90th percentile for age and sex had a positive predictive value of 0.88 for iron sufficiency. This study demonstrates that diminished iron stores in cyanotic congenital heart disease are associated with a more right-shifted oxyhemoglobin dissociation curve (increased P50).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of iron deficiency on tissue oxygen delivery in cyanotic congenital heart disease. 334 85

We hypothesized that children with cyanotic congenital heart disease and moderate hypoxemia, as a result of erythrocytosis, and adequate iron stores would have low serum erythropoietin titers, low tissue oxygen delivery, and normal red cell 2,3-diphosphoglycerate (DPG) concentrations. We assessed hemoglobin levels, aortic oxygen saturation, iron stores, red cell 2,3-DPG, oxygen consumption, and systemic O2 transport in 19 hypoxemic patients, aged 3 months to 8 years. Low erythropoietin titers (less than 30 mU/dl) were found in 14 patients. Patients with high erythropoietin titers had lower Pao2 (36 +/- 7 vs 49 +/- 7 mm Hg, p less than 0.01), lower aortic saturation (68 +/- 12 vs 81 +/- 9%, p less than 0.01), and higher red cell 2,3-DPG (2.47 +/- 0.34 vs 3.23 +/- 0.73 mumol/ml, p less than 0.01). Aortic oxygen saturation higher than 80% was associated with a low erythropoietin titer and a hemoglobin level below that associated with hyperviscosity. The relationship between aortic oxygen saturation and hemoglobin concentration was strong (r = 0.77). These data suggest that for children less than 8 years of age, adequate compensation for moderate hypoxemia can occur with moderate increases in hemoglobin levels.
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PMID:Erythropoietin in cyanotic heart disease. 339 15

The relation between degree of cardiac functional impairment and changes in hemoglobin-oxygen affinity and 2,3-diphosphoglycerate (2,3-DPG) has been studied in 39 patients with noncyanotic heart disease. A progressive decline in hemoglobin-oxygen affinity was found with worsening cardiac function as assessed by cardiac index, arteriovenous oxygen (A-V O(2)) difference, and cardiac symptoms; this alteration in hemoglobin-oxygen binding represents a significant mechanism for adaptation to the limited oxygen supply imposed by the cardiac lesion. The highly significant correlation of mixed venous blood oxygen saturation (S[unk]V(VO2)) with 2,3-DPG and the position of the oxygen dissociation curve suggests that the level of deoxygenated hemoglobin is an important in vivo regulator of hemoglobin-oxygen affinity.
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PMID:The effect of cardiac disease on hemoglobin-oxygen binding. 543 70

An increase in hemoglobin concentration characterizes the normal compensatory response to chronic tissue hypoxia. We observed no such increase in 42 chronically hypoxic patients with cystic fibrosis, in whom the mean concentration was 12.6 gm/dl; one third of the patients were anemic. Compared with patients with cyanotic heart disease, patients with cystic fibrosis did not have a compensatory increase in P50 or 2,3-diphosphoglycerate. Despite anemia, erythropoietin levels in patients with cystic fibrosis were not significantly different from normal control values. The growth of colony-forming units-erythroid in patients with cystic fibrosis was similar to that in control subjects, and there was no inhibition of growth with the addition of autologous serum. Erythropoietin sensitivity, determined by measuring the CFUe dose response curve, was normal in both patients and controls. Results of iron studies were consistent with iron deficiency in the majority of patients. Impaired absorption of iron was observed in six of 13 iron-deficient patients with cystic fibrosis. An inverse correlation between erythrocyte sedimentation rate and peak serum iron was obtained during the iron absorption study. Eight patients who underwent a therapeutic trial of iron demonstrated a 1.8 gm/dl rise in hemoglobin concentration. Two patients with previously documented iron malabsorption responded to parenteral iron therapy after failure to respond to oral supplementation. These studies demonstrate that patients with cystic fibrosis not only have an impaired erythroid response to hypoxia, but are frequently anemic. Their inadequate erythroid response to hypoxia results in part from disturbances in erythropoietin regulation and iron availability.
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PMID:Inadequate erythroid response to hypoxia in cystic fibrosis. 673 32

The amount of oxygen delivered to an organ depends on three factors: blood flow and its distribution; the oxygen-carrying capacity of the blood, i.e. haemoglobin concentration; and oxygen extraction. Non-haemodynamic and haemodynamic mechanisms operate to compensate for anaemia. Non-haemodynamic mechanisms include increased erythropoietin production to stimulate erythropoiesis, and increased oxygen extraction (displacement of the haemoglobin oxygen dissociation curve). This decreased affinity of oxygen for haemoglobin is mediated by increased 2,3-diphosphoglycerate concentrations. Increased cardiac output is the main haemodynamic factor, mediated by lower afterload, increased preload, and positive inotropic and chronotropic effects. Decreased afterload is due to vasodilatation and reduced vascular resistance as a consequence of lower blood viscosity, hypoxia-induced vasodilatation, and enhanced nitric oxide activity. Vasodilatation also involves recruitment of microvessels and, in the case of chronic anaemia, stimulation of angiogenesis. With decreased afterload, the venous return (preload) and left ventricular (LV) filling increase, leading to increased LV end-diastolic volume and maintenance of a high stroke volume and high stroke work. High stroke work is also due to enhanced LV contractility attributed to increased concentrations of catecholamines and non-catecholamine inotropic factors. In addition, heart rate is increased in anaemia, due to hypoxia-stimulated chemoreceptors and increased sympathetic activity. In the long term, these haemodynamic alterations lead to gradual development of cardiac enlargement and LV hypertrophy (LVH). The LVH is eccentric, characterized by increased LV internal dimensions and a normal ratio of wall thickness to cavity diameter, as occurs in other forms of volume overload. When anaemia-related LVH develops in an otherwise 'healthy' humoral environment, the lesions are reversible and the type of LVH is primarily physiological and is not associated with impaired diastolic function. In the absence of underlying cardiovascular disorders, severe anaemia (Haemoglobin concentration < 4-5 g/dl) leads to congestive heart failure. In the presence of heart disease, especially coronary artery disease, anaemia intensifies angina and contributes to a high incidence of cardiovascular complications. In end-stage renal disease (ESRD), LVH is influenced by many other factors, leading to intense interstitial fibrosis, to alterations in diastolic function, and usually to poor reversibility. The chronic increase in cardiac output contributes to arterial remodelling of central elastic arteries such as the aorta and common carotid artery. This remodelling consists principally of arterial enlargement and compensatory arterial intima--media thickening. In ESRD, these geometric changes are accompanied by arterial stiffening. The principal consequences of arterial alterations are increased systolic pressure and high inertia due to higher blood mass in the dilated arterial system. These alterations contribute to the development of LVH and abnormal coronary perfusion.
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PMID:Pathophysiology of anaemia: focus on the heart and blood vessels. 1103 52

Two male castrated Whippet littermates were presented at 1 year of age for pallor, tachycardia, systolic heart murmur, dark yellow to orange feces, intermittent lethargy, pigmenturia, and muscle shivering or cramping after exercise. Persistent macrocytic hypochromic anemia with marked reticulocytosis and metarubricytosis was found when CBC results were compared with reference values for Whippets. Increased serum creatine kinase activity and hyperkalemia also were sometimes present over the 4-year period of evaluation. Progressively increasing serum concentrations of N-terminal prohormone brain natriuretic peptide suggested cardiac disease. Erythrocytes from the whippets were less osmotically fragile but more alkaline fragile than those from control dogs. Erythrocyte phosphofructokinase (PFK) activities and 2,3-diphosphoglycerate concentrations were decreased. Restriction enzyme-based DNA test screening and DNA sequencing revealed the same mutation in the muscle-PFK gene of the Whippets as seen in English Springer Spaniel dogs with PFK deficiency. This is the first report of PFK deficiency in Whippet dogs. In addition to causing hemolysis and exertional myopathy, heart disease may be a prominent clinical component of PFK deficiency in this breed and has not been previously recognized in PFK-deficient English Springer Spaniels.
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PMID:Hemolysis, myopathy, and cardiac disease associated with hereditary phosphofructokinase deficiency in two Whippets. 1922 57